Hepatitis B virus (HBV) infection is a global health problem. While HBV has not been propagated in any tissue culture system or animals except in man and in chimpanzees, laboratory testing for the hepatitis B surface antigen (HBsAg) by blood banks has revealed chronic HBV infection and varying degrees of liver disease in a large number of apparently healthy persons. The 'e' antigen (HBeAg) correlates with a high degree of infectivity and a high amount of HBsAg, which in a purified form has served the purpose of HBV-vaccines. The safety and efficacy of the candidate vaccines has been established in chimpanzees prior to their use in man. Alternate vaccines consisting of polypeptide components of HBsAg may be advantageous because they are devoid of viral DNA, host proteins, lipoproteins and glycoproteins. However, the polypeptides are poorly immunogenic and require use of physiologically acceptable adjuvants. We propose to investigate large scale production of an immunogenic 22,000 daltons structural polypeptide of HbsAg (P-22), to investigate various procedures for coupling P-22 to purified tetanus toxoid (PT-tox) and to evaluate the end products for their toxicity and their ability to produce high titered antibodies to HBsAg. The principle of immunologic cooperation in carrier-primed hosts will be utilized by immunization of animals with normal tetanus toxoid, followed by hyperimmunization with the conjugates of PT-tox and P-22. This sequence should produce enhanced immune response to the P-22/HBsAg. A satisfactorily immunogenic conjugate of PT-tox-P-22 could provide a reliably noninfectious immunogen, obviating the need for continued safety testing in chimpanzees. If, indeed, this goal is achieved, the potential application of the so called "U.C.-Vaccine" for prophylactic immunization as well as immunointervention in chronic HbsAg carrier state may become feasible.